Immune function declines with advancing age. The resultant morbidity and mortality in aged individuals is a considerable cost burden on the health care system. Thus, interventions designed to enhance the immune function in the aged are important. There is abundant evidence that the neuroendocrine system, via its numerous mediators, influences the immune system. Moderate exercise-training leads to production of the various neuroendocrine mediators and has been shown to enhance several in vitro immune responses in young and aged animals. Since moderate physical exercises can enhance B and T cell function in young and aged mice, the investigators will test the hypothesis that moderate exercise-training can enhance the in vivo humoral and cell mediated immunity in young and aged mice. Preliminary studies have shown that moderate exercise-training can enhance secondary antibody response in young mice. The intent of this proposal, is to study the effects of moderate exercise-training on in vivo humoral and cell-mediated immune responses in young and aged mice by evaluating the humoral and cell-mediated immune responses in a mouse model of lymphocytic choriomeningitis virus (LCMV) infection. Studies outlined in this proposal will provide preliminary data that shows exercise has a significant impact on the immune system of aged mice. This data will then be used in an R01 proposal to develop a mechanistic investigation of how exercise affects this change. Additionally, studies to examine whether prevention of age-related decline in immune function can be accomplished by starting mice on an exercise program during their middle age are proposed. A long-term goal is to develop therapeutic exercise protocols that enhance immunocompetence with aging.